CRP

Should I order serum procalcitonin on my patient with suspected infection?

FA Manian MD, MPH, , , , , , , , , , , 2 Comments

Two things to ask before you order procalcitonin (PCT): 1. Will it impact patient management?; and 2. If so, will the result be available in a timely manner ie, within hours not days?

Whatever the result, PCT should always be interpreted in the context of the patient’s illness and other objective data. Not surprisingly then, as a “screening” test, PCT may be more useful in patients with low pre-test likelihood of having bacterial infection, not dissimilar to the use of D-dimer in patients with low pre-test probability of pulmonary embolism1.  

Several potential clinical uses of this biomarker have emerged in recent years,  including:1,2

  • Helping decide when to initiate antibiotics in patients with upper acute respiratory tract infections and bronchitis. A normal or low PCT supports viral infection.
  • Helping decide when to discontinue antibiotics (ie, when PCT normalizes) in community-acquired or ventilator-associated pneumonia.
  • Helping monitor patient progress with an expected drop in PCT of about 50% per day (half-life ~ 24 hrs) with effective therapy.

Few caveats…

  • PCT may be unremarkable in about a third of patients with bacteremia (especially due to less virulent bacteria, including many gram-positives)3.  
  • PCT levels are lowered by high-flux membrane hemodialysis, so check a baseline level before, not after, hemodialysis4.
  • Lastly, despite its higher specificity for bacterial infections compared to other biomarkers such as C-reactive protein, PCT may be elevated in a variety of non-infectious conditions, including pancreatitis, burns, pulmonary edema or aspiration, mesenteric infarction (ischemic bowel), cardiogenic shock, and hypotension during surgery2.

 

References:

  1. Schuetz P, Muller B, Chirst-Crain M, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections (review). Evid-Based Child Health (A Cochrane Review Journal) 2013;8:4;1297-137. http://onlinelibrary.wiley.com/doi/10.1002/ebch.1927/pdf
  2. Gilbert GN. Use of plasma procalcitonin levels as an adjunct to clinical microbiology. J Clin Microbiol 2010;48:2325-29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897488/pdf/0655-10.pdf
  3. Yan ST, Sun LC, Jia HB. Procalcitonin levels in bloodstream infections caused by different sources and species of bacteria. Am J Emerg Med 2017;35:779-83. https://www.ncbi.nlm.nih.gov/m/pubmed/27979420/#fft
  4. Grace E, Turner RM. Use of procalcitonin in patients with various degrees of chronic kidney disease including renal replacement therapy. Clin Infect Dis 2014;59:1761-7. https://www.ncbi.nlm.nih.gov/pubmed/25228701
Should I order serum procalcitonin on my patient with suspected infection?

My patient with cirrhosis has been admitted to the hospital several times this year with bacterial infections. How does cirrhosis increase susceptibility to infections?

FA Manian MD, MPH, , , , , , , , Leave a comment

Bacterial infections are a common cause of morbidity and mortality in patients with cirrhosis, affecting about 30% of such patients either at admission or during their hospitalization, with an attendant risk of mortality that is twice that of individuals without cirrhosis1.

Two major mechanisms may account for the observed immune dysfunction in cirrhosis: 1. Compromise of the immune surveillance function of the liver itself through damage of the reticulo-endothelial system (RES) and reduced synthesis of innate immunity proteins and pattern recognition receptors (PRRs); and 2. Dysfunctions of circulating and intestinal population of immune cells2.

Damage to the RES in cirrhosis leads to portal-system shunting, loss/damage of Kupffer cells (specialized hepatic macrophages) and sinusoidal capillarization, all hindering blood-borne pathogen clearance. Cirrhosis is also associated with a defect in hepatic protein synthesis, including complement components, decreased PRRs and acute phase reactants (eg C-reactive protein), which may in turn lead to the impairment of the innate immunity and bacterial opsonization.

Cirrhosis can also cause reduction in the number and function of neutrophils (eg, decreased phagocytosis and chemotaxis), B, T, and NK lymphocytes, and decreased in bacterial phagocytosis by monocytes. In addition, damage to the gut-associated lymphoid tissue (eg Peyer’s patches and mesenteric lymph nodes) may facilitate bacterial translocation.

References

  1. Pieri G, Agarwal B, Burroughs AK. C-reactive protein and bacterial infections in cirrhosis. Ann Gastroenterol 2014;27:113-120. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982625/pdf/AnnGastroenterol-27-113.pdf
  2. Albillos A, Lario M, Alvarez-Mon M. Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance. J Hepatol 2014;61:1385-1396. http://www.journal-of-hepatology.eu/article/S0168-8278(14)00549-2/pdf

 

My patient with cirrhosis has been admitted to the hospital several times this year with bacterial infections. How does cirrhosis increase susceptibility to infections?

My patient with cirrhosis and suspected infection has a normal serum C-reactive protein (CRP). Does cirrhosis affect CRP response to infection?

FA Manian MD, MPH, , , , , , , , Leave a comment

CRP is primarily synthesized by the liver mainly as a response to IL-6 production in inflammatory states1.  Lower CRP production may then be expected in cirrhotic patients with significant infections and several studies support this view2. 

In a particularly convincing study involving E. coli-infected patients with bacteremia, the median CRP level in cirrhotic patients was about 40% that of non-cirrhotic patients (62 mg/L vs 146 mg/L)3.  In another study involving bacteremic patients with or without liver dysfunction, median CRP level was about 60% that of  patients with preserved liver function (81 mg/L vs 139 mg/L)4. 

Some investigators have reported a cut-off CRP value of 9.2 mg/L as a possible screening test for bacterial infections in patients with cirrhosis with a sensitivity and specificity of 88% (AUROC 0.93)5.

Collectively, these data suggest that although CRP response may be diminished in patients with advanced liver disease and acute infection, its synthesis is still maintained.

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 References

  1. Pieri G, Agarwal B, Burroughs AK. C-reactive protein and bacterial infection in cirrhosis. Ann Gastroenterol 2014;27:113-20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982625/pdf/AnnGastroenterol-27-113.pdf
  2. Ha YE, Kang C-I, Joo E-J, et al. Usefulness of C-reactive protein for evaluating clinical outcomes in cirrhotic patients with bacteremia. Korean J Intern Med 2011;26:195-200. http://pubmedcentralcanada.ca/pmcc/articles/PMC3110852/pdf/kjim-26-195.pdf
  3. Park WB1, Lee KD, Lee CS et al. Production of C-reactive protein in Escherichia coli-infected patients with liver dysfunction due to liver cirrhosis. Diagn Microbiol Infect Dis. 2005 Apr;51(4):227-30. https://www.ncbi.nlm.nih.gov/pubmed/15808312
  4. Mackenzie I, Woodhouse J. C-reactive protein concentrations during bacteraemia: a comparison between patients with and without liver dysfunction. Intensive Care Med 2006;32:1344-51. https://www.ncbi.nlm.nih.gov/pubmed/16799774
  5. Papp M, Vitalis Z, Altorjay I, et al. Acute phase proteins in the diagnosis and prediction of cirrhosis associated bacterial infection. Liver Int 2011;603-11. https://www.ncbi.nlm.nih.gov/pubmed/22145664

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

My patient with cirrhosis and suspected infection has a normal serum C-reactive protein (CRP). Does cirrhosis affect CRP response to infection?

When should I suspect spinal epidural abscess in my 55 year old patient with severe back pain?

FA Manian MD, MPH, , , , , Leave a comment

 It cannot be overemphasized that up 50% of patients with spinal epidural abscess (SEA) have no known risk factors,  one-half may have no fever,  and 20-40% lack leukocytosis1. In fact, the “classic triad” of back pain, fever, and neurological deficits is found only in the minority of patients!  No wonder that up to 75% of patients SEA are misdiagnosed on their initial healthcare encounter1!

Potential “red flags” for infectious causes of low back pain include age >50 y, night pain, unremitting pain even when supine, duration > 6 weeks, fever, chills, night sweats, weight loss, conditions associated with Staphylococcus aureus bacteremia (eg intravenous drug use), incontinence, saddle anesthesia, and severe or rapidly progressive neurologic deficits1,2.  

ESR and C-reactive protein (CRP) are almost uniformly elevated in SEA1 and can serve as a good starting point in excluding this condition when in doubt.   In patients ≥50 y of age with low back pain, obtaining ESR routinely has been suggested for detection of systemic disease (eg cancer, infection)3.  Similarly, in a recent algorithm of severe back pain, routine measurements of ESR and CRP, even in the absence of any neurological findings, has been recommended1; elevation of either may necessitate consideration of MRI.

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References:

  1. Bond, A, Manian FA. Spinal epidural abscess: a review with special emphasis on earlier diagnosis. BioMed Res International 2016; https://www.hindawi.com/journals/bmri/2016/1614328/http://dx.doi.org/10.1155/2016/1614328  
  2. Della-Giustina. Acute low back pain: recognizing the “red flags” in the workup. Consultant 2013;53:436-440. http://www.consultant360.com/article/acute-low-back-pain-recognizing-%E2%80%9Cred-flags%E2%80%9D-workup
  3. Jarvik JG, Deyo RA. Diagnostic evaluation of low back pain with emphasis on imaging. Ann Intern Med 2002;137:586-597. http://annals.org/aim/article/715687/diagnostic-evaluation-low-back-pain-emphasis-imaging

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers, Mass General Hospital, Harvard Medical School or its affiliated institutions. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Additional disclosure: The author of this post (FAM) also coauthored reference 1.

When should I suspect spinal epidural abscess in my 55 year old patient with severe back pain?

Is there a seasonal variation in the incidence of cardiovascular (CV) events or venous thromboembolism (VTE)?

FA Manian MD, MPH, , , , , , , , , , 1 Comment

Seasonal variation, primarily characterized by a winter peak, has been reported for acute CV events, such as acute myocardial infarction (AMI) and sudden death, aortic rupture or dissection, and ischemic or hemorrhagic stroke, and VTE (1). A meta-analysis involving patients with VTE, primarily with a diagnosis of pulmonary embolism, revealed a 20% absolute increase in the incidence of VTE during January (1).  

Potential physiological mechanisms for these observations include increased sympathetic activity, decreased loss of fluids and sodium, increase in LDL cholesterol, increase in serum fibrinogen levels and other coagulation markers and C-reactive protein, and lower vitamin D levels due to shorter daylight hours during winter months (1,2).  At least in the case of AMI in the U.S., the higher incidence in winter is not affected by climate (2).  

Respiratory virus infections as a cause of acute inflammation leading to  CV or VTE events is another intriguing explanation (3). Indeed, influenza vaccination has been associated with reduction in hospitalization for cardiac disease and stroke among the elderly (4) and, in patients with cardiovascular disease, a reduction in death due to combined cardiovascular disease events such as heart attacks and strokes (5).

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References

  1. Dentali F, Ageno W, Rancan E, et al. Seasonal and monthly variability in the incidence of venous thromboembolism. A systematic review and a meta-analysis of the literature. Thromb Haemost 2011;106:439-447. https://www.ncbi.nlm.nih.gov/pubmed/21725580
  2. Spencer FA, Goldberg RJ, Becker RC, et al. Seasonal distribution of acute myocardial infarction in the Second National Registry of Myocardial Infarction. J Am Coll Cardiol 1998;31:1226-33.h ttps://www.ncbi.nlm.nih.gov/pubmed/9581712
  3. Woodhouse PR, Khaw KT, Plummer M, et al. Seasonal variations of plasma fibrinogen and factor VII activity in the elderly: winter infections and death from cardiovascular disease. Lancet 1994;343:435-39.  https://www.ncbi.nlm.nih.gov/pubmed/7508540
  4. Nichol KL, Nordin J, Mulloly J, et al. Influenza vaccination and reduction in hospitalization for cardiac disease and stroke among the elderly. N Engl J Med 2003; 348:1322-1332. http://www.nejm.org/doi/full/10.1056/NEJMoa025028
  5. Clar C, Oseni Z, Flowers N, et al. Cochrane Database of Systematic Reviews 2015. DOI: 10.1002/14651858.CD005050.pub3h ttp://www.cochrane.org/CD005050/VASC_flu-vaccines-for-preventing-cardiovascular-disease  

 

 

 

 

Is there a seasonal variation in the incidence of cardiovascular (CV) events or venous thromboembolism (VTE)?

How do I interpret an elevated serum C-reactive protein (CRP) and normal erythrocyte sedimentation rate (ESR) or vice-versa?

FA Manian MD, MPH, , , , , , , , , , , , Leave a comment

Discordance between serum CRP and ESR is not uncommon (1,2). This phenomenon may be due to a variety of factors including the fact that the kinetics of these two tests is quite different, as discussed in another P4P Post.

In a study of CRP/ESR discordance (defined as results differing by 2 or 3 quartiles) in adults, a high CRP/low ESR profile was more likely to be associated with  urinary, GI, blood stream, and pulmonary infections, myocardial infarction, and venous thromboembolism and less likely to be associated with bone and joint infections (1).

In the same study, a high ESR/low CRP was associated with connective tissue diseases, such as systemic lupus erythematosus and strokes (1).

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References

1. Feldman M, Aziz B, Kang GN, et al. C-reactive protein and erythrocyte sedimentation rate discordance: frequency and causes in adults. Translational Research 2013;161:37-43. https://www.ncbi.nlm.nih.gov/pubmed/22921838

2. Colombet I, Pouchot J, Kronz V. Agreement between erythrocyte sedimentation rate and C-reactive protein in hospital practice. Am J Med 2010;123:864.e7-863.e13.https://www.ncbi.nlm.nih.gov/pubmed/20800157

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers, Mass General Hospital, Harvard Medical School or its affiliated institutions. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

How do I interpret an elevated serum C-reactive protein (CRP) and normal erythrocyte sedimentation rate (ESR) or vice-versa?

How should follow-up serum C-reactive protein (CRP) in patients with community-acquired pneumonia (CAP) be interpreted?

FA Manian MD, MPH, , , Leave a comment
CRP level should drop to less than one-half of its value on admission after a couple of days of antibiotic therapy, since CRP half-life is less than a day following zero order elimination kinetics. 

 

Of interest, in a study of serial CRP in severe CAP (1), a CRP ratio >0.5 by day 3 was associated with non-resolving pneumonia ( sensitivity 91%, specificity 55%)   performing significantly better than body temperature or WBC count.  

 

So if there is any doubt about how a patient is doing clinically, a repeat CRP looking for a drop of greater than on-half after 3-4 days of therapy may be helpful.

 

Bonus Pearl: Did you know that the half-life of CRP is 19 h?

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Reference

1. Coelho L, Povoa P, Almenda E, et al. Usefulness of C-reactive protein in monitoring the severe community-acquired pneumonia clinical course.  Critical Care 2007;11:R92 https://ccforum.biomedcentral.com/articles/10.1186/cc6105

 

 

How should follow-up serum C-reactive protein (CRP) in patients with community-acquired pneumonia (CAP) be interpreted?